Pregnanolone effects on the blood pressure of stress-induced hypertension in rats

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1 Acta Physiologica Sinica August June (3) (4) http// 471 * (pregnanolone ) (stress-induced hypertension SIH) (0.24 mg/kg) (angiotensin Ang ) Fos (FLI) 1 h 1 h+ 15 d 15 d+ 15 d+ 15 d (P<0.001) 1 h 15 d Ang ( P<0.001); 1 h+ 15 d+ Ang 1 h 15 d ( P<0.05); 15 d Ang 1 h (P<0.05) 15 d 15 d+ FLI 1 h (LHb) (MHb) (PVN) (CeA) (LH) FLI 1 h SIH Ang ; ; ; Fos Q463 Pregnanolone effects on the blood pressure of stress-induced hypertension in rats LI Man-Song ZHAO Hua * XIA Ying-Hong Department of Physiology School of Basic Medical Sciences Jilin University Changchun Jilin China Abstract This study was conducted to determine the effect of pregnanolone () on blood pressure of a rat model of stress-induced hypertension (SIH). This model was established by applying electric shock to animal feet together with noise. was administered intraperitoneally at 0.24 mg/kg d -1 and blood pressure angiotensin (Ang ) levels and the expression of Fos-like protein immunoreactive (FLI) neurons in brain areas were determined. Rats were randomly divided into five groups (1) control (2) stressed for 1 h (3) stressed for 1 h after pretreatment (4) stressed for a 2 h session twice a day for 15 d and (5) stressed for a 2 h session after pretreatment twice a day for 15 d. The results showed that increased systolic pressure of tail artery caused by a 15-d stress treatment was significantly reduced by pretreatment (P<0.001). Ang levels measured by radioactive immunoreactivity were significantly elevated (P<0.001) after the rats were stressed for 1 h or 15 d the Ang level was significantly reduced by treatment in both 1 h and 15 d stress groups (P<0.05). Only a small number of FLI neurons were found in the brain areas of the control group 15 d stress group and 15 d stress with group. In the 1 h stress group more FLI neurons were found in the lateral habenular nucleus the medial habenular nucleus the paraventricular nucleus the central nucleus of amgydaloid and the lateral hypothalamus compared with the control group. pretreatment significantly prevented the increase in the number of FLI neurons. These results indicate that pretreatment prevents elevation of tail artery systolic pressure in SIH rats and that this effect of may be mediated through reducing Ang level and inhibiting the activity of cardiovascular center involved in stress. Key words pregnanolone; stress-induced hypertension; angiotensin ; Fos-like protein Received Accepted This work was supported by the Science Foundation of Jilin Province (No ). Corresponding author. Tel ; Fax ; zhaohua_1957@hotmail.com

2 472 Acta Physiologica Sinica August (4) one) [1] (pregnanolone 5β-pregnan-3α-ol-20- [2] [34] γ- (GABA) GABA CI γ- (GABA)/ (BZD) GABA [5] GABA CI (angiotensin Ang ) Ang [6-8] Ang (stress-induced hypertension SIH) Ang SIH Ang Wistar g 1 h 1 h+ 15 d 15 d+ 1 h 1 h 2~4 ma 50 ms (80~100 Bs 50 ms) ; 1 h mg/kg; 15 d 2 2 h 15 d ; 15 d mg/ kg.d -1 Sigma Ang 1.4 Fos 1 h 15 d 10% 10 d LKB 5 µm Paxinos Watson PBS 5 min 3 ( A) 15 min PBS 50 µl ( B) 30 min c-fos 4ºC PBS 50 µl ( C) 25 min PBS 50 µl - ( D) 25 min PBS PBS DAB mean SD t h 1 h mmhg (n=8) mmhg (n=8)

3 473 (P>0.05); 15 d mmhg (n=8) mmhg (P< d mmhg (n=8) mmhg 15 d (P <0.001) ( 1) <0.05); 15 d Ang 1 h (P<0.05 2) 2. Ang 1. Fig. 1. Effects of stress stimulation on tail sysolic pressure in i.p. treaed and non-treaed rats. * P>0.05 ** P<0.05 compared with control group *** P<0.001 compared with stress 15 d+ group. 2.2 Ang 1 h 15 d Ang 1 h 15 d Ang pg/ ml (n=8) pg/ml (n=8) ( pg/ml n=6) ( P<0.001); 1 h+ 15 d+ Ang pg/ml (n=8) pg/ ml (n=8) 1 h 15 d ( P Fig. 2. Effects of stress stimulation on contents of Ang in plasma with i.p. -treaed and non-treaed rats. a P<0.05 b P<0.001 compared with control group c P<0.001 compared with stress 1 h+ group d P<0.001 compared with stress 15 d+ group. 2.3 FLI 15 d 15 d + Fos (FLI) 1 h (LHb) (MHb) (PVN) (CeA) (LH) FLI 1 h ( 1) 1. 1 h 1 h+ Table 1. Percentage of expression in different brain regions of control 1 h stress and 1 h stress + groups Control (n=6) Stress 1 h (n=8) Stress 1 h+ (n=8) LHb 4.5% ± 0.3% 39.7% ± 10.6% * 20.2% ± 8.9% * MHb 1.5% ± 0.2% 18.2% ± 6.9% * 11.2% ± 5.4% * PVN 2.2% ± 0.3% 48.2% ± 13.9% * 25.2% ± 9.8% * CeA 3.5% ± 0.5% 28.9% ± 7.8% * 17.2% ± 6.3% * LH 1.5% ± 0.3% 27.3% ± 8.1% * 21.2% ± 6.9% * * P<0.001 compared with control groups; P<0.05 P<0.001 compared with stress 1 h+ groups.

4 474 Acta Physiologica Sinica August (4) [67] 15 d [9] 15 d Ang 1 h (RAS) Ang SIH [3] [16] [710] Ang 15 d SIH Ang 5 min Fos 20~30 min 60~90 min 2~5 h [11] [12] Fos 1 h PVN CeA (LH) FLI Ceccatelli S [1314] (PVN) (CRF) - - (HPA) CeA LH 1 h SIH [16] - [15] Ang LHb MHb LHb MHb [17] LHb MHb MHb [18] LHb LHb 15 d 15 d+ Fos (FLI) Ang A * * * Pickering TG. Mental stress as a causal factor in the development of hypertension and cardiovascular disease. Curr Hpertens Rep 2001;3(3) Costa E Auta J Guidotti A Korneyev A Romeo E. The pharmacology of neurosteroidogenesis. J Steroid Biochem Mol Biol 1994;49(4-6) Devaud LL Purdy RH Morrow AL. The neurosteroid 3αhydroxy-5α-pregnan-20-oneprotects against bicuculline-induced seizures during ethanol withdrawal in rats. Alcohol Clin Exp Res 1995; Purdy RH Morrow AL Moore PH Paul SM. Stress-induced elevations of γ-aminobutyric acid type A receptor-active steroids in the rat. Proc Nael Acad Sci USA 1991; Smith GB Olsen RW. Functional domains of receptors. Trends Pharmacol Sci 1995; 16(5) Wan Y ( ) Yang G Wan SX Yang B Yin YR Xi ZX. Renin-angiotensin system-stress hormone response system. Acta Physiol Sin ( ) 1996;48(6) (Chinese

5 475 7 Lu LM ( ) Wang J Yao T. Angiotensin participates in stress-induced high blood pressure via stimulating hypothalamic vasopressin synthesis and release. Acta Physiol Sin( ) 2000;52(5)371~374 (Chinese 8 Cui JJ ( ) Wang S Zhang Y. Effects of intracerebroventricular injection of angiotensin on blood pressure and discharges of habenula nucleus cardiovascular neurons. Acta Physiol Sin ( ) 2000;52(4) (Chinese English abstract). 9 Lu LM ( )Wang JYao T.Changes in vasopressin V 1 receptor mrna level in rats with high blood pressure induced by chronic stress. Acta Physiol Sin ( ) (4) Liu D ( ) Yang G Lu JS. Changes of the content of angiotensin in plasma and tissues in stress-indued hypertensive. Chin J Arterioscler ( ) 1998; 6(2) (Chinese 11 Xue BJ ( ) Zhang XX Shi GM He RR. Increased expression of in the brainstem nuclei involved cardiova scular regulation by capsaicin. Acta Physiol Sin( ) 2000; 52(2) (Chinese ; Ceccatelli S Villar MJGolstein M Hokfelt T. Expression of c- fos immunoreactivity in transmitter-characterized neurons after stress. Proc Natl Acad Sci USA1989; Xu S ( ) Jiang XH Guo SY Yu GD Yin QZ Hisamitsu T. Induction of fos protein expression in rat brain by water immersion-restraint stress and footshock stress. Chin J Appl Physiol 1999;15(4) Chinese English abstract(. 15 Amold EJDe Lucas Bueno MShiers H. Expression of in regions of the basal limbic forebrain following ICV CRF in unstressed or stressed male rats.neuroscience 1992; Li MS ( ) Zhao H. Effect of intracerebroventricular injection of BGN on the cardivovascular response in stress-induced hypertension rats. J Jilin Univ ( ) 2003; (Chinese 17 Zhao H ( ) Wang S. Research on the cardiovascular response pattern elicited by excitation of habenula. J N Bfthune Univ Med Sci ( ) 1994; (Chinese 18 Zhao H ( ) Yang W Wang S Jin YX. Relationship between blood pressure and pain threshold changes induced by exciting respectively medial and lateral habenular nucleus. Chin J Appl Physiol ( ) 1995; 11(4) (Chinese